Abstract

Recent literature has argued the superiority of radial access compared with femoral access for percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Three particular trials—RIVAL (Radial Versus Femoral Access for Coronary Intervention), RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome), and STEMI-RADIAL (ST Elevation Myocardial Infarction Treated by Radial or Femoral Approach–Randomized Multicenter Study Comparing Radial Versus Femoral Approach in Primary PCI)—demonstrated lower rates of bleeding and vascular complications with the transradial approach. Bleeding is a major independent predictor of negative long-term outcomes including death, predisposes patients to transfusions, and attenuates the ability to administer cardioprotective post-procedural anticoagulation. These trials, however, employed suboptimal antithrombotic practices. Namely, the dose of heparin and percent of patients on glycoprotein IIb/IIIa inhibitors were unnecessarily high, and a paucity of patients were on bivalirudin, which decreases bleeding and improves outcomes compared with heparin and glycoprotein IIb/IIIa inhibitors. The use of larger gauge catheters in femoral access patients predisposed them to major bleeding and its subsequent complications. In addition, these trials were carried forth in high-volume transradial centers, further limiting the ability to generalize the findings to most PCI centers. These are important considerations especially for high-risk and ACS patients, in whom the negative implications of major bleeding are even greater. Without an optimized design, the applications of the trial findings are uncertain. Ultimately, a trial comparing femoral versus radial access in patients on bivalirudin, potent oral antiplatelet medication, and without adjunctive glycoprotein IIb/IIIa inhibitors is needed to assess outcomes based on access site alone.

The benefits of early invasive treatment with percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) are well accepted (1,2). However, recent literature has challenged the common practice of attaining access via the femoral artery, arguing the superiority of radial access in terms of bleeding and mortality, and calling for a paradigm shift in the approach of interventionalists (3–9). Though the published evidence favoring radial access is compelling, there exist fundamental limitations in the methodology of these studies. Namely, the administration of antithrombotic agents was either excessive, inappropriate, or both. Here, we offer insight into and special consideration to these trials with reconsideration of the femoral approach.

Anticoagulation: The Forgotten Variable

Antithrombotic dose

In the United States, as many as 32% of patients receive antithrombotic doses in excess of guidelines (11). In patients with STEMI being referred for primary PCI, the American College of Cardiology Foundation/American Heart Association guideline recommends a 50- to 70-IU/kg bolus to achieve an activated clotting time of 200 to 250 s when use of glycoprotein IIb/IIIa receptor antagonists are planned and a 70- to 100-U/kg bolus to achieve an activated clotting time of 250 to 300 s (as measured by the HemoTec device [Medtronic, Parker, Colorado]) when no glycoprotein IIb/IIIa inhibitor use is planned (12). Heparin doses in excess of this have not been associated with improved pre-procedural patency or post-procedural outcomes, but have been associated with greater bleeding (13). The average dose of pre-procedural heparin was 71 IU/kg in the RIFLE-STEACS trial and, more egregiously, 104 IU/kg in STEMI-RADIAL, doses higher than current guideline recommendations when glycoprotein IIb/IIIa inhibitors are used because low-dose heparin is equally effective (4,5,12,13).

Antithrombotic drug

The ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) trial demonstrated significantly less bleeding with the direct thrombin inhibitor bivalirudin compared with heparin and glycoprotein IIb/IIIa inhibitors at 30 days (3.0% vs. 5.7%, p < 0.001) in patients with ACS undergoing an invasive strategy (14). The HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, which compared STEMI patients randomized to heparin plus glycoprotein IIb/IIIa inhibitors or bivalirudin, reported a 34% reduction in mortality in patients treated with bivalirudin (p = 0.047), driven by a reduction in major bleeding of 40% (p < 0.001) that was similarly seen in a subsequent large meta-analysis (15,16). In both the radial and femoral arms, a paucity of patients received bivalirudin (RIVAL: 2.2% and 3.1%, respectively; RIFLE-STEACS: 8.0% and 7.2%, respectively) despite the evidence showing that bivalirudin attenuates bleeding events by one-half without additional ischemic complications (3,4,14,15). The importance of this cannot be ignored; bleeding independently predicts ischemic complications, transfusion, and death (17,18).

Presumably, the differences in bleeding and mortality relate in part to the aggressive use of glycoprotein IIb/IIIa inhibitors—approximately one-third in the RIVAL trial, nearly half in the STEMI-RADIAL trial, and over two-thirds in the RIFLE STEACS trial—predisposing to bleeding and vascular complications in the large-caliber femoral artery in which larger sheaths were used.

Lower doses of heparin, decreased use of potent parenteral antiplatelet agents, and increased use of bivalirudin could ultimately reduce bleeding and need for transfusions. This would permit continuation, not only of post-procedural oral antiplatelet drugs, but also of other cardioprotective agents, lessening the risk for subsequent cardiac compromise (a main determinant of mortality in the femoral access approach). These considerations are particularly relevant in high-risk ACS patients, in whom the larger femoral artery may be necessary anyway for device insertion such as an intra-aortic balloon pump.

Procedural characteristics are also affected by the choice of access site. Door-to-balloon and fluoroscopy times tend to be less with the femoral approach, and choice of sheath size is less restrictive (3–5). Outcomes with vascular closure devices have evolved over time, but recent meta-analyses have noted they may safely reduce femoral bleeding, further reducing the gap in bleeding and mortality outcomes between access sites (19).

Finally, the prospective randomized trials supporting the radial approach were all done at high-volume radial access centers. Indeed, the RIVAL study demonstrated no difference in the lower 2 tertiles of operator experience (3). This is an important consideration in the United States, where <7% of PCI procedures are accessed radially (11,20).

Conclusions

At first glance, current studies support the benefits of radial access PCI in ACS. These conclusions, however, are drawn from patients on suboptimal antithrombotic regimens as well as liberal use of potent parenteral antiplatelet agents. Thus, the influence of access site alone on outcomes cannot be accurately measured. Ultimately, a trial comparing femoral versus radial access in patients treated with bivalirudin or appropriate doses of heparin, novel P2Y12 receptor inhibitors such as prasugrel or ticagrelor and without adjunctive glycoprotein IIb/IIIa inhibitors, is needed to assess outcomes on the basis of access site alone. The ongoing SAFARI-STEMI (the Safety and Efficacy of Femoral Access Versus Radial for Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction) trial (NCT01398254) will help shed light into this particular topic. Until further data emerge, femoral access with optimal pharmacotherapy should be considered a safe, viable and time-tested option for PCI access in ACS.

Footnotes

Dr. Lee has received honoraria from Abiomed, St. Jude Medical, Medtronic, and Boston Scientific. Dr. Stone has served as a consultant to Boston Scientific. Dr. Wolfe has reported that he has no relationships relevant to the contents of this paper to disclose.

(2009) Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. Am Heart J157:132–140.

(2012) A contemporary view of diagnostic cardiac catheterization and percutaneous coronary intervention in the United States: a report from the CathPCI Registry of the National Cardiovascular Data Registry, 2010 through June 2011. J Am Coll Cardiol60:2017–2031.